TEAD1 (TEA Domain Transcription Factor 1)

These findings establish NRG4 as a metastasis suppressor in obesity-associated breast cancer by inhibiting the ERBB4-YAP1 pathway and down-regulating matrix metalloproteinases. Our study highlights the therapeutic potential of targeting NRG4-ERBB4 signaling to mitigate obesity-driven breast cancer progression.

Our findings indicate that while molecular weight and TPSA influence CNS penetration, efflux transporter interactions are more predictive of brain exposure. MSC-4070 represents a promising candidate for targeting TEAD-driven tumors in the central nervous system.

Using CRISPR/Cas9-mediated knockout and rescue experiments in EOC cell lines, we demonstrate that MED12 deficiency significantly enhances sensitivity to ferroptosis inducers (RSL3 and Erastin), as evidenced by reduced IC50 values...Pharmacological inhibition of YAP with verteporfin or siRNA-mediated TEAD1 knockdown reverses ferroptosis sensitivity in MED12-deficient cells, confirming pathway specificity. These findings establish MED12 as a modulator of the YAP-TEAD1-ferroptosis axis and suggest that targeting this pathway could overcome chemoresistance in MED12-deficient EOC. Our work provides a mechanistic foundation for exploiting ferroptosis induction as a therapeutic strategy in ovarian cancer.

We provide a detailed toolkit for structural, biophysical and cellular profiling, including the development of a cellular target engagement assay for the lipid pocket of TEAD1 and an IAP/TEAD1 ternary complex formation assay. Our study therefore provides essential resources for detailed characterization of IAP-recruiting degraders and important tools and learnings for bifunctional degraders targeted to the lipid pocket of TEADs.

This study indicates that there are causal links between the gut microbiota and PCa. Feature genes may affect the occurrence of PCa by inhibiting the epithelial-mesenchymal transition, proliferation, migration, and invasion of cells.

Importantly, two clinical drugs, the RhoA inhibitor simvastatin and the YAP1/TEAD inhibitor verteporfin were determined to be the disruptors of this feed-forward signaling axis, inhibiting ICC tumor growth. These findings reveal the vital function of ANLN in ICC growth and provide promising treatment strategies for ICC.

The anti-proliferative and pro-apoptotic activities are achieved by the simultaneous inhibition of the Hippo-YAP and JAK2/STAT3 signaling pathways. These results underline the potential of RLN2 as a therapeutic target for treatment of advanced cervical cancer and necessitate further applied research to investigate its clinical use.

CUR treatment downregulated YAP1 and TEAD1, and upregulated p-YAP1 and apoptosis-related proteins both in vivo and in vitro. In conclusion, CUR could alleviate gastric mucosal inflammation and prevent the occurrence and progression of GPL, potentially via modulation of the YAP/TEAD axis in the Hippo signaling pathway.

Additionally, we identified that the TEA domain transcription factor 1 (TEAD1)-derived peptide effectively disrupted YAP condensate formation, leading to AMPKα activation in vivo and inhibition of primary liver cancer progression. This study systematically confirms that YAP phase separation plays a crucial role in the progression of various primary liver cancers and further substantiates that strategic disruption of these condensates constitutes an effective treatment for primary liver cancer in vivo.

Overall, these findings suggest that MEG-01-derived EVs approximate certain aspects of megakaryocyte-lineage exosomes and activated platelet-like states, although they do not fully replicate native platelet biology. Notably, plasma exosomes show strong proteomic convergence with MEG-01 exosomes, whereas platelet exosomes retain distinct activation-related features.

We identify a novel CD155/YAP/TEAD1/GLUT1 axis that reprograms LUAD metabolism and facilitates immunosuppressive tumor microenvironment formation. CD155 functions as a metabolic-immune hub in LUAD, and its targeting could simultaneously suppress tumor growth and restore antitumor immunity, offering dual therapeutic advantages. Clinically, 18F-FDG PET/CT represents a noninvasive biomarker for CD155-driven metabolic aggression, potentially guiding precision immunotherapy.

Our findings unveil a sophisticated spatial paradigm of liver regeneration following radiation injury, wherein spatially partitioned hepatocyte subpopulations deploy compartmentalized repair programs to balance proliferative efficiency and metabolic adaptation, suggesting potential new targets for therapeutic intervention against RILI.